Despite their physiological and therapeutical importance, our understanding of the ligand-induced molecular mechanisms of GPCR activation is hampered by the relative scarcity of structural data. In the last 12 years, advances in protein engineering, crystallization methods and X-ray crystallography techniques have allowed the determination of more than 100 crystal structures of 20 different GPCRs in complex with ligands of varied pharmacology, peptides and with other proteins.
In my research I aim to understand how extracellular ligands trigger the process of signal transduction in GPCRs. Using a combination of structural bioinformatics, molecular dynamics and data-mining of structure and sequence databases, I extract as much information as possible from experimentally determined protein structures. This knowledge is used to design new experiments and to build experimentally testable models of GPCR function that will lead to a better understanding of ligand selectivity and efficacy.
I am particularly interested in determine the molecular principles of ligand selectivity (i.e. how specific ligands recognize certain receptors), efficacy (i.e. how ligands activate GPCRs) and biased signaling (i.e. how specific ligands preferentially trigger certain signaling pathways).
Molecular signatures of G-protein-coupled receptors
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM.
Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II
Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J.
Proceedings of the National Academy of Sciences USA 2012 Jan 3;109(1):119-24
Tracking G-protein-coupled receptor activation using genetically encoded infrared probes
Ye, S., Zaitseva, E., Caltabiano, G., Schertler, G. F. X., Sakmar, T. P., Deupi, X., and Vogel, R.
Nature 2010 464, 1386–1389